For the use only of a Registered Medical Practitioner or a Hospital or a Laboratory

IU/mL

Insulin Glargine Injection (rDNA)

TM
BASALOG Refil
3 mL Cartridges

Insulin glargine is a recombinant Human insulin analogue that is a long-acting (up to 24 hour duration of action), • If your INSUPen® with the cartridge inside is in cold storage, take it out 1 to 2 hours before you inject to allow it to
parenteral blood-glucose-lowering agent. warm up. Cold insulin is more painful to inject.
• To prevent contamination always use a new pen needle for each injection.
Solution for injection in a cartridge, for subcutaneous use only.
BASALOG RefilTM 3mL cartridges are available in the strength of 100 IU/mL for use with INSUPen® (re-usable injector) TM
Do not use BASALOG Refil cartridge
only. • In insulin infusion pumps.
• If the cartridge or the INSUPen® containing the cartridge is dropped, damaged or crushed there is a risk of leakage
Composition: of insulin.
Each mL contains • If it has not been stored correctly or if it has been frozen.
Insulin glargine (rDNA) 100 IU • If the liquid appears cloudy, coloured or has some suspended matter.
m-cresol 2.7 mg (as preservative)
Excipients q.s. Preparation and Handling:
(Each 100 units is equivalent to 3.64 mg insulin glargine) BASALOG RefilTMshould be inspected visually prior to administration. BASALOG RefilTMmust only be used if the
solution is clear and colourless with no visible particles.
Pharmaceutical form
A clear colourless solution for injection in cartridge. Mixing and diluting:
BASALOG RefilTMmust not be diluted or mixed with any other insulin or solution.
Description:
Insulin glargine differs from human insulin in that the amino acid asparagine at position A21 is replaced by glycine and Contraindications:
two arginines are added to the C-terminus of the B-chain. Chemically, it is 21A Gly-30Ba-L-Arg-30Bb-L-Arg-human insulin BASALOG RefilTMis contraindicated in patients hypersensitive to the active substance or to any of the excipients.
and has the empirical formula C267H404N72O78S6 and a molecular weight of 6063.
Warnings:
Indications: Hypoglycaemia is the most common adverse effect of insulin, including insulin glargine. As with all insulins, the timing
BASALOG RefilTM is indicated for the treatment of adults, adolescents and children of 6 years or above with diabetes of hypoglycaemia may differ among various insulin formulations. Glucose monitoring is recommended for all patients
mellitus, where treatment with insulin is required. with diabetes.

Dosage and method of administration: Any change of insulin should be made cautiously and only under medical supervision. Changes in insulin strength,
Insulin glargine is an analogue of human insulin which exhibits a relatively constant glucose lowering profile over 24 timing of dosing, manufacturer, type (e.g., regular, NPH, or insulin analogues), species (animal, human), or method of
hours that permits once-daily dosing. Potency of insulin glargine is approximately the same as human insulin. manufacture (recombinant DNA versus animal source insulin) may result in the need for a change in dosage.
Concomitant oral anti-diabetic treatment may need to be adjusted.
BASALOG RefilTMis recommended for once daily subcutaneous administration and may be administered at any time
during the day. However, once started it should be administered at the same time every day. For patients requiring BASALOG RefilTMcontains m-cresol , which may cause Type IV(delayed hypersensitivity) allergic reactions.
change in dosing and timing with BASALOG RefilTM: see Warnings and Precautions. BASALOG RefilTMis not
recommended for intravenous administration (see Precautions). Intravenous administration of the usual subcutaneous Precautions:
dose could result in severe hypoglycaemia. The desired blood glucose levels as well as the doses and timing of other anti- General:
diabetic medications must be determined individually. Blood glucose monitoring is recommended for all patients with Patients must be advised that BASALOG RefilTMmust NOT be diluted or mixed with any other insulin or solution.
diabetes. Patients should be instructed on self-management procedures including glucose monitoring, proper injection
technique, and hypoglycaemia and hyperglycaemia management. Patients must be instructed on handling of special
The prolonged duration of action of BASALOG RefilTM is dependent on injection into subcutaneous space. As with all situations such as intercurrent conditions (illness, stress, or emotional disturbances), an inadequate or skipped insulin
insulins, injection sites within an injection area (abdomen, thigh, or deltoid) must be rotated from one injection to the dose, inadvertent administration of an increased insulin dose, inadequate food intake, or skipped meals. As with all
next. patients who have diabetes, the ability to concentrate and/or react may be impaired as a result of hypoglycaemia or
hyperglycaemia. Patients with diabetes should be advised to inform their health care professional if they are pregnant or
In published clinical studies, there was no relevant difference in insulin glargine absorption after abdominal, deltoid, or contemplating pregnancy.
thigh subcutaneous administration. As for all insulins, the rate of absorption, and consequently the onset and duration
of action, may be affected by exercise and other variables. Timing of insulin doses is extremely important. The best approach is to measure blood glucose and add a dose of regular
insulin if glucose levels are too high. Otherwise, wait for the next scheduled dose. Do not stop taking insulin injections
BASALOG RefilTM is not the insulin of choice for the treatment of diabetes ketoacidosis. An intravenous short-acting unless advised by your doctor.
insulin is the preferred treatment.
Insulin glargine is not intended for intravenous administration. The prolonged duration of activity of insulin glargine is
Initiation of BASALOG RefilTM therapy: dependent on injection into subcutaneous tissue. Intravenous administration of the usual subcutaneous dose could
Depending on the need of basal insulin appropriate amount of BASALOG RefilTM should be used as basal insulin result in severe hypoglycaemia. Insulin glargine must not be diluted or mixed with any other insulin or solution. If insulin
component and the post prandial insulin requirements should be taken care of by using short acting/rapid acting glargine is diluted or mixed, the solution may become cloudy, and the pharmacokinetic/pharmacodynamic profile (e.g.,
premeal insulin. onset of action, time to peak effect) of insulin glargine and/or the mixed insulin may be altered in an unpredictable
Based on published information the recommended starting dose for type 2 diabetic patients who are not on insulin is manner. When insulin glargine and regular human insulin are mixed immediately before injection there is a possibility of
10 IU once daily on average and subsequently adjusted according to the patient's need to a total daily dose ranging from delayed onset of action and delayed time to maximum effect for regular human insulin. The total bioavailability of the
2 to 100 IU, however doses needs to be individualized by the prescriber for a particular patient. mixture may also slightly decreased compared to separate injections of insulin glargine and regular human insulin. As
with all insulin preparations, the time course of insulin glargine action may vary in different patients or at different times
Paediatric use: in the same patient and the rate of absorption is dependent on blood supply, temperature, and physical activity. Insulin
Insulin glargine can be administered to children >6　
years of age. Administration to children <6 years has not been may cause sodium retention and oedema, particularly if previously poor metabolic control is improved by intensified
studied. insulin therapy.

Geriatric use: Hypoglycaemia:

In elderly patients with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to The time of occurrence of hypoglycaemia depends on the action profile of the insulins used and may, therefore, change
avoid hypoglycaemic reactions. Hypoglycaemia may be difficult to recognize in the elderly. when the treatment regimen is changed. As with all insulins, particular caution should be exercised in patients in whom
sequelae of hypoglycaemic episodes might be of particular clinical relevance; and intensified blood glucose monitoring
Changeover to BASALOG RefilTM: is advisable. Early warning symptoms of hypoglycaemia may be different or less pronounced under certain conditions,
If changing from a treatment regimen with an intermediate or long-acting insulin to a regimen with BASALOG RefilTM, such as long duration of diabetes, diabetes nerve disease, use of medications such as beta-blockers, or intensified
the amount and timing of short-acting insulin or fast-acting insulin analogue or dose of any oral anti-diabetic drug may diabetes control. Such situations may result in severe hypoglycaemia (and, possibly, loss of consciousness) prior to the
need to be adjusted. patients' awareness of hypoglycaemia. Compliance of the patient with the dosage and dietary regimen, correct insulin
administration and awareness of hypoglycaemia symptoms are essential to reduce risk.
Based on the published clinical studies it is recommended that:
• If transferring patients from once-daily NPH insulin to once-daily BASALOG Refil T M , the Renal impairment:
recommended initial glargine dose should be the same as the dose of NPH that is being discontinued. BASALOG RefilTMrequirements may be diminished because of reduced insulin metabolism, based on observations with
• If transferring patients from twice-daily NPH insulin to once-daily BASALOG RefilTM, the recommended initial other insulins.
BASALOG RefilTMdose should be 80% of the total NPH dose that is being discontinued. This dose reduction will
lower the likelihood of hypoglycaemia Hepatic impairment:
BASALOG RefilTM requirements may be diminished due to reduced capacity for gluconeogenesis and reduced insulin
A program of close metabolic monitoring under medical supervision is recommended during transfer and in the initial metabolism, similar to other insulins.
weeks thereafter. The amount and timing of short-acting insulin or fast acting insulin analogue may need to be
adjusted. This is particularly true for patients with acquired antibodies to human insulin needing high-insulin doses and Intercurrent conditions:
occurs with all insulin analogues. Dose adjustment of insulin glargine and other insulins or oral anti-diabetes drugs may Intercurrent illness requires intensified metabolic monitoring in many cases. A urine test for ketones is indicated, and
be required; for example, if the patient's timing of dosing, weight or lifestyle changes, or other circumstances arise that often it is necessary to adjust the insulin dose. The insulin requirement is often increased. In patients with type 1
increase susceptibility to hypoglycaemia or hyperglycaemia. The dose may also have to be adjusted during intercurrent diabetes, carbohydrate supplies must be maintained even if patients are able to eat only little or no food, or are vomiting
illness (see Precautions). etc.; in patients with type 1 diabetes insulin must never be omitted entirely.

Instructions to be given to the patient on how to handle BASALOG RefilTMcartridge Drug interactions
1. The BASALOG RefilTMcartridges are designed to be used with INSUPen®. Detailed instruction accompanying the A number of drugs are known to interact with insulin with respect to glucose metabolism and may require dose
INSUPen® must be followed. adjustment of insulin glargine.
2. If the patient is treated with BASALOG RefilTMcartridge and another insulin cartridge, two INSUPen®
should be used, one for each type of insulin. Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to hypoglycaemia include
3. The BASALOG RefilTMcartridges are for single person use only, and should not be shared with oral antidiabetic agents, angiotensin converting enzyme (ACE) inhibitors, disopyramide, fibrates, fluoxetine,
monoamine oxidase (MAO) inhibitors, pentoxifylline, propoxyphene, salicylates and sulfonamide antibiotics.
anyone else.
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, diazoxide, diuretics,
4. The BASALOG RefilTMcartridges are not to be refilled.
glucagon, isoniazid, oestrogens and progestogens, phenothiazine derivatives, somatropin, sympathomimetic agents
(e.g. epinephrine [adrenaline], salbutamol, terbutaline), thyroid hormones, atypical antipsychotic medicinal products
Before using BASALOG RefilTMcartridge
(e.g. clozapine and olanzapine) and protease inhibitors.
• Check the label to make sure it is the right type of insulin.
• Remove the cartridge from the blister pack by pushing through the foil side of the Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the blood glucose lowering effect of
packaging. insulin. Pentamidine may cause hypoglycaemia, which may sometimes be followed by hyperglycaemia.
• Appearance of air bubble is a normal phenomenon, vigorous shaking immediately before the dose is
administered may also result in the formation of air bubbles which could cause dosage errors; in that case tap the In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, guanethidine and
container gently with your finger. A small air bubble may remain in the cartridge after taping; this small air bubble reserpine, the signs of adrenergic counter-regulation may be reduced or absent.
will not affect your dose.
• Detailed instruction accompanying the INSUPen® must be followed.

1
 For the use only of a Registered Medical Practitioner or a Hospital or a Laboratory

IU/mL

Insulin Glargine Injection (rDNA)

TM
BASALOG Refil
3 mL Cartridges

Pregnancy and lactation Pharmacokinetics:

Pregnancy: Absorption and bioavailability: Serum concentrations after subcutaneous injection of insulin glargine in healthy subjects
There are no well-controlled clinical studies of the use of insulin glargine in pregnant women. It is essential for patients and in patients with diabetes, indicated a slower, more prolonged absorption and a relatively constant
with diabetes or a history of gestational diabetes to maintain good metabolic control before conception and throughout concentration/time profile over 24 hours, with no pronounced peak in comparison to NPH human insulin. In published
pregnancy. Insulin requirements may decrease during the first trimester, generally increase during the second and third studies, the duration of action was similar after subcutaneous administration in the abdomen, deltoid, or thigh.
trimesters, and rapidly decline after delivery. Careful monitoring of glucose control is essential in such patients.
Metabolism: In a published study in humans it was found that insulin glargine is partly metabolized at the carboxyl
Nursing mothers: terminus of the B chain in the subcutaneous depot to form two active metabolites with in vitro activity similar to that of
It is unknown whether insulin glargine is excreted in human milk. Because many drugs, including human insulin, are insulin, M1 (21A-Gly-insulin) and M2 (21A Gly des 30B Thr insulin). Unchanged drug as well as these degradation
excreted in human milk, caution should be exercised when insulin glargine is administered to a nursing woman. Use of products were present in the circulation.
insulin glargine is compatible with breastfeeding, but women with diabetes who are lactating may require adjustments
of their insulin doses. Clinical studies - efficacy results
Efficacy of Biocon's insulin glargine was assessed in a phase III study conducted by Biocon Limited to establish safety and
Effects on the ability to drive and use machines non-inferiority (in comparison to reference product), with respect to decrease in HbA1C in patients with type 1 diabetes
The patient’s ability to concentrate and react quickly may be impaired as a result of, for example, hypoglycaemia or mellitus.
hyperglycaemia or as a result of visual impairment. This may constitute a risk in situations where these abilities are of
special importance (e.g. driving a car or operating machinery). The results established non-inferiority of Biocon's insulin glargine compared to the reference product, with respect to
change in HbA1c. The changes in FPG, PPG and seven-point glucose were comparable between the two study arms. The
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is particularly important in proportion of patients who achieved target HbA1c <7% was comparable between groups. Mean insulin dose was also
those who have reduced or absent awareness of the warning signs of hypoglycaemia. The feasibility of driving should be comparable between the two arms. Compliance was good during the study, with average compliance >98% for both
considered in these circumstances. basal & pre meal soluble insulin which was comparable for both study arms.

Undesirable effects: Overall the two study treatments were comparable with respect to efficacy.
In a clinical study done by Biocon the adverse events were similar in nature, frequency, and severity as compared to the
reference product. Preclinical safety data
Hypoglycaemic events were the most common adverse events in both the treatment groups. Apart from Based on published literature insulin glargine is reported to be non mutagenic in a series of in vitro and in vivo
hypoglycaemia, pyrexia was the next most common adverse event with three events in each study arm. Retinal adverse genotoxicity assays.
events reported in this study were comparable between the treatment groups. The abnormalities in the laboratory
parameters were comparable between the two study arms and all of them were considered not clinically significant. Based on conventional non clinical (acute and repeat dose toxicity) studies performed with BASALOG RefilTM, the non
Antibodies against Biocon's insulin glargine were observed with the same frequency as compared to the reference clinical data reveals no special hazard for humans.
product.
Pharmaceutical particulars
Following are the adverse events reported in published literature for insulin glargine: List of excipients
Hypoglycaemia: Zinc chloride
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the insulin dose is too high Glycerin
in relation to the insulin requirement. As with all insulins, severe hypoglycaemic episodes may be life-threatening. In m-cresol
many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic counter-regulation. Sodium hydroxide (for pH adjustment)
Generally, the greater and more rapid the decline in blood glucose, the more marked is the phenomenon of counter Hydrochloric acid (for pH adjustment)
regulation and its symptoms. Water for injection.

Eye disorders: Incompatabilities

A marked change in glycaemic control may cause temporary visual impairment, due to temporary alteration in the In general terms insulin should only be added to compounds with which it is known to be compatible.
turgidity and refractive index of the lens. Long-term improved glycaemic control decreases the risk of progression of
diabetic retinopathy. However, intensification of insulin therapy with abrupt improvement in glycaemic control may be Shelf life
associated with temporary worsening of diabetic retinopathy. In patients with proliferative retinopathy, particularly if Please refer to the expiry data on label/carton.
not treated with photocoagulation, severe hypoglycaemic episodes may result in transient amaurosis. Never use BASALOG RefilTM after the expiry date printed on the pack.

Injection site and allergic reactions: Storage and precautions:

As with any insulin therapy, lipodystrophy may occur at the injection site and delay insulin absorption. Other injection Store BASALOG RefilTMcartridge in a refrigerator at temperature between 2°C and 8°C. It should not be allowed to
site reactions with insulin therapy include redness, pain, itching, hives, swelling, and inflammation. Continuous rotation freeze.
of the injection site within a given area may help to reduce or prevent these reactions. Most minor reactions to insulins
usually resolve in a few days to a few weeks. The solution can be kept at room temperature (below 25°C) for up to 28 days once the cartridge has been put to use.

In published clinical studies, using regimens, which included insulin glargine, injection site reactions were observed in 3 Do not expose to excessive heat or direct sunlight.
to 4% of patients. As with any insulin therapy, such reactions include redness, pain, itching, hives, swelling and
inflammation. Most minor reactions to insulins usually resolve in a few days to a few weeks. Immediate-type allergic Keep BASALOG RefilTM cartridge out of reach of children.
reactions are rare. Such reactions to insulin (including insulin glargine) or the excipients may, for example, be associated
with generalized skin reactions, angioedema, bronchospasm, hypotension, or shock and may be life threatening. Do not use frozen BASALOG RefilTMcartridge.

Immune system disorders: DO NOT MIX WITH OTHER INSULINS OR SOLUTION.

Insulin administration may cause insulin antibodies to form.
Nature and contents of container:
Nervous system disorders: Dysgeusia (taste disorders) The solution is presented in glass cartridge (USP type 1). It is sealed using lined seals and plugged with plunger stopper.
1x3mL, 3x3mL or 5x3mL cartridges are packed in a carton.
Musculoskeletal and connective tissue disorders: Myalgia
Special precautions for disposal and handling
Overdose Any unused product or waste material should be disposed of in accordance with local regulations.
A specific overdose of insulin cannot be defined. However, hypoglycaemia may develop over sequential stages:
Manufactured by:
• Mild hypoglycaemic episodes can be treated by oral administration of glucose or sugary products. It is therefore Biocon Limited
recommended that the diabetic patients carry some sugar lumps, sweets, biscuits or sugary fruit juice. Biocon Special Economic Zone,
Plot No. 2-4, Phase IV, Bommasandra-Jigani Link Road,
• Severe hypoglycaemic episodes, where the patient has become unconscious, can be treated by glucagon (0.5 to 1 Bommasandra Post, Bangalore – 560 099.
mg) given intramuscularly or subcutaneously by a person who has received appropriate instruction, or by glucose
given intravenously by a medical professional. Glucose must also be given intravenously if the patient does not Marketed by:
respond to glucagon within 10 to 15 minutes. Biocon Limited
20th KM Hosur Road, Electronics City, Bangalore – 560100.
Upon regaining consciousness, administration of oral carbohydrate is recommended for the patient in order to prevent
relapse. For further details, please contact:
Medical Advisor
Pharmacological properties Biocon Limited,
Pharmacotherapeutic group: Insulins and analogues for injection, long-acting. ATC Code: A10AE04. Semicon Park, Tower II, Electronics City Phase II,
Bangalore – 560100.
Mechanism of action:
Primary function of insulin, including insulin glargine, is regulation of glucose metabolism. Insulin and its analogues Leaflet revised August 2011
lower blood glucose levels by stimulating peripheral glucose uptake, primarily by skeletal muscle and fat, and by
inhibiting hepatic glucose production. Anabolic functions of insulin include inhibition of lipolysis, inhibition of TM - Trade mark.
proteolysis, and enhancement of protein synthesis.
To get product related information and/or to report adverse events, visit our website www.biocon.com or call our
Pharmacodynamics: customer care service WINNING WITH DIABETES on the toll free no: 1800-425-7667.
Insulin glargine has low aqueous solubility at neutral pH. At pH 4, as in the insulin glargine injection solution, it is
completely soluble. After injection into the subcutaneous tissue, the acidic solution is neutralized, leading to formation To report adverse events, you can also email us at [email protected].
of microprecipitates from which small amounts of insulin glargine are slowly released, resulting in a relatively constant
concentration/time profile over 24 hours with no pronounced peak. This allows once-daily dosing as a patient's basal
BF0341/03

insulin.

In published clinical studies, the glucose-lowering effect on a molar basis of intravenous insulin glargine was
approximately similar to human insulin. In published euglycaemic clamp studies, both in healthy subjects or in patients
with type 1 diabetes, the onset of action of subcutaneous insulin glargine was slower than NPH human insulin. The
effect profile of insulin glargine was relatively constant with no pronounced peak and the duration of its effect was
prolonged compared to NPH human insulin.